there is considerable motivation and justification for suggesting that the use of singly housed rhesus macaques may complicate interpretations of normal immunological responses. This may
have important implications for the management, treatment, and selection of primate subjects for immunological studies. q 2000 Elsevier Science B.V. All rights reserved.
Keywords: Primate housing; Immune response; Macaca mulatta
1. Introduction
Housing captive primates socially, either in pairs or in groups, usually results in Ž
behavioral benefits for the animals so housed Crockett et al., 1994; Reinhardt, 1994; .
Ž Schapiro et al., 1996a,b . While this is not always the case Coe, 1991; Ruppenthal et
. al., 1991; Crockett et al., 1994; Clarke et al., 1995 , if group or pair mates are properly
Ž chosen and attention is paid to other relevant psychosocial variables Reinhardt, 1989,
1994; Reinhardt et al., 1988, 1995; Crockett et al., 1994; Schapiro and Bloomsmith, .
1994; Schapiro et al., 1996a , social housing can be an extremely effective enrichment strategy, providing numerous opportunities for the expression of species-typical behav-
Ž .
iors Bramblett, 1989; Mason, 1991; Novak and Suomi, 1991 . Behavioral measures provide important information about subjects’ psychological well-being in these types of
studies, but it is also important to attempt to correlate behavioral measures with physiological measures, to further illustrate the relevance of the variables being manipu-
lated and assessed.
A number of investigators have examined the effects that psychosocial variables can Ž
have on immunological responses in captive macaques Boccia et al., 1992; Cohen et al., 1992; Gust et al., 1992; Coe, 1993; Terao et al., 1995; Capitanio et al., 1996, 1998a;
. Clarke et al., 1996; Schapiro et al., 1998 . A large proportion of these efforts have
examined the effects of manipulations to the social environments of the subjects, with Ž
many of these analyzing the effects of mother–infant separations Coe et al., 1988, .
1989; Laudenslager et al., 1990; Terao et al., 1995 . One normally observes diminished Ž
immune function in response to stressful social manipulations Cohen et al., 1992; .
Ž Gordon et al., 1992; Coe, 1993; Lubach et al., 1995 . As described previously Schapiro
. Ž .
et al., 1998 , immune responses typically measured include: 1 lymphocyte subset
q q
Ž levels, primarily CD4
and CD8 Gust et al., 1991; Gordon et al., 1992; Lubach et al.,
. Ž . 1995; Capitanio et al., 1998a; Lilly et al., 1999 ; 2 lymphocyte proliferation responses
Ž .
Kaplan et al., 1991; Boccia et al., 1992; Cohen et al., 1992; Lubach et al., 1995 ; and Ž .
Ž .
Ž 3 natural killer cell NK activity Boccia et al., 1992; Lubach et al., 1995; Terao et al.,
. 1995 .
Since nonhuman primates are currently used in a variety of immunological studies ŽVillinger et al., 1993; Benveniste et al., 1996; Capitanio et al., 1998b; Gold et al., 1998;
. Nehete et al., 1998; Marcario et al., 1999; Sarkar et al., 1999 , we feel that it is crucial
to quantify the effects that behavioral management strategies, such as single housing during experiments, have on the immunological responses of captive primates. Work by
Ž .
Capitanio et al. 1998b emphasizes the importance of behavioral management tech- niques in biomedical research and will be briefly described. In their investigation, some
Ž singly caged rhesus macaques were allowed to spend regular periods 100 minrsession,
. 3–5 sessionsrweek interacting in stable social groups, while the remaining subjects
Ž .
spent regular periods same duration and frequency as above interacting in social groups whose membership was constantly altered by the experimenters. Capitanio et al.
Ž .
1998b found that the macaques that had been in stable social groups spent significantly more time in affiliative interactions and had significantly longer survival times after
Ž .
infection with simian immunodeficiency virus SIV than macaques that had been in Ž
unstable social groups. They concluded that psychosocial factors the social opportuni- ties and relationships provided by interacting with a stable set of partners, specifically
. the amount of time spent affiliating , could influence a critical immunological factor,
Ž .
survival time after infection with a deadly pathogen SIV . This finding highlights the relevance of psychosocial factors and their effects on laboratory primates in biomedical
research. Nonhuman primate subjects for biomedical research are usually chosen in a fairly
nonsystematic fashion. Typically, available andror inexpensive animals are chosen first Ž
. Kaplan et al., 1991; Benveniste et al., 1996 , with little regard for other factors. Prior to
the beginning of an experiment, monkeys are removed from their ‘‘normal’’ housing and placed in the experimental condition. A period of acclimation to allow the subjects
to adapt to their new surroundings is usually provided. The acclimation period can vary Ž
. in duration from several weeks to several months Capitanio et al., 1996 , but is rarely
rigidly controlled or explicitly stated. There are few empirical data that demonstrate that an acclimation period of a specific length is necessary for subjects to return to baseline
Ž .
functioning. In fact, recent work by Lilly et al. 1999 shows that acclimation is unlikely to have occurred, even 28 weeks after removal from the ‘‘normal’’ housing condition.
Clearly, an enhanced understanding of the time course of acclimation processes would be germane to biomedical research with laboratory primates.
Ž . We were specifically interested in determining 1 whether there were any differences
in the cell-mediated immune responses of adult rhesus monkeys that were housed singly, Ž .
in pairs, or in small groups and 2 whether these responses changed over time. Clearly, housing adult rhesus monkeys individually is a fairly stressful psychosocial manipula-
tion; one that may be comparable to the more commonly studied mother–infant separation or reintroduction to groups of conspecifics. We measured lymphocyte sub-
sets, mitogen- and pathogen-induced lymphocyte proliferation, NK activity, and cy- tokine production on multiple occasions over a 12-month period. Measuring lymphocyte
proliferation responses to gastrointestinal pathogens is a novel approach with potential ecological relevance.
2. Animals, materials, and methods
