Soluble Mlsa antigens: Stimulatory effect in vitro versus suppressive effect in vivo

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Abstract
Using a pair of congenic strains of mice differing only at the Mls haplotype (Mls locus and closely linked genes), BALB/c (Mls b ) and BALB.D2-Mls a , we have compared the in vitro proliferative responses of M1sb lymphocytes to M1sa antigens presented on either lymph node cells (LNC) or peritoneal adherent cells (PAC). Results showed that M1sa-PAC are stronger stimulators than M1sa-LNC, and furthermore, that the supernatant from M1sa-PAC may be effective in eliciting a lymphocyte proliferative response. The proliferation in response to PAC supernatant is partially due to activation by nonspecific factor(s); however, the response in the presence of M1sa incompatible PAC supernatant is about three times greater than the response obtained in the presence of syngeneic M1sb-PAC supernatant, suggesting an additional stimulation by soluble M1sa antigens. Contrasting with the ability of PAC-supernatant to stimulate a primary proliferative response in vitro, the in vivo immunization of Mlsb mice with M1sa-PAC supernatant abrogates the specific proliferative response in subsequent one-way mixed lymphocyte cultures. This abrogation of the specific response is comparable to that observed after immunization with intact M1sa peritoneal or spleen cells, although in the latter case the anti-H-2 proliferative response is also decreased, regardless of whether the H-2 incompatible stimulating cells express an additional incompatibility for M1sa. The proliferation of untreated, but not of M1sa-immunized BALB/c LNC, is stronger in cultures with DBA/2 stimulating cells (incompatible for M1sa and other non-H-2 antigens) than in cultures with BALBM-Mls a cells (incompatible for M1sa alone), and is comparable in intensity to that activated by H-2 incompatibility. We conclude that M1sa antigens are more efficiently recognized by unprimed helper T cells when presented on PAC than when presented on LNC. In the primary proliferative response, the effects of M1sa and other non-H-2 antigens may be cumulative. In vivo immunization against M1sa antigens results in suppression of the specific proliferative response and, to a certain extent, of the nonspecific proliferative response (directed against both H-2 and other non-H-2 antigens). Since M1sa antigens are obtainable in soluble form, their physicochemical purification can now be envisaged.