Functional analysis of lymphocytes subpopulations in experimental cocaine abuse. I. Dose-dependent activation of...

The potential role of substance abuse, especially cocaine and alcohol as co-factor in HIV infection and in the development and expression of AIDS has been suggested, but the possible biological role of substance abuse in the development of AIDS is not known. In order to better understand immune system function in chronic cocaine abuse, we have assessed primary B cell responses to helper T-cell independent (TI) and dependent (TD) antigens in inbred Fisher male rats injected with 1.25-5 mg cocaine/kg body weight for 10 days. The ability of cocaine-exposed animals to mount primary in vivo splenic plaque-forming cell (PFC) and serum antibody responses to the TI antigen, pneumococcal polysaccharide type III (SIII), was elevated several-fold when compared with controls. The degree of elevation of humoral antibody responses seemed to be directly related to the dose of cocaine. Primary in vivo B cell responses to the TD antigen, sheep red blood cells (SRBC), was elevated at lower concentrations of cocaine (1.25-2.5 mg/kg) and was found to be significantly suppressed after chronic exposure to the higher concentration (5.0 mg/kg). The elevated primary splenic immunostimulation to TI (SIII) may be attributed to a combination of loss of T suppressor cell control and direct B cell stimulation. Elevated immune responses to SRBC at lower concentrations were attributed to stimulation of T helper cells as well as loss of T suppressor cells. Immunosuppression to SRBC observed in response to 5.0 mg/kg of cocaine was most probably due to loss of T helper cell subset functions. These findings were further tested by in vitro methods, where splenic lymphocytes from cocaine-exposed animals were examined for their ability to respond to concanavalin A (Con A) in terms of the induction of antigen non-specific suppressor T cells. The addition of Con A-stimulated splenic lymphocytes from cocaine-treated animals did not inhibit the primary antibody responses of SRBC as compared with saline-treated controls, indicating that suppressor T cells malfunction after cocaine exposure. Lymphocyte subpopulation analysis using fluorescein-labelled monoclonal antibodies showed a significant increase in the B cell populations at doses of 1.25-5 mg/kg. A reciprocal change in T cell populations also took place. No significant numerical change in macrophage (NSE+) and T cell subset, T helper and T suppressor was noticed, suggesting that cocaine probably directly effects mature T cell subset functions but does not affect their differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)