CYTOKINE RESPONSE IN MULTIPLE LYMPHOID-TISSUES DURING THE PRIMARY PHASE OF FELINE IMMUNODEFICIENCY VIRUS-INFECTION

Type 1 and 2 cytokine mRNA responses were measured at various time per iods and in various lymphoid compartments during the acute stage (firs t 4 months) of feline immunodeficiency virus (FIV) infection in labora tory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i .) onward, peaked at 56 to 70 days, and declined greatly by 70 days. V irus replication was highest in the thymus, followed by spleen, mesent eric lymph nodes, and cervical lymph nodes. Baseline cytokine levels w ere highest in the mesenteric lymph nodes and lowest in the cervical l ymph nodes. Cytokine upregulation after FIV infection was most dramati c in the cervical lymph nodes, with the greatest increase in interleuk in-10 (IL-10) and gamma interferon (IFN-gamma). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-gamma, IL-12p40, IL-4, and IL-10, while elevations in the sple en were mainly for IFN-gamma, IL-12p40 and IL-10. An increase in IFN-g amma, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., conco mitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues te sted, CD4(+) cells were the primary source of IL-2, IL-4, and IL-10. B oth CD4(+) and CD8(+) cells produced IFN-gamma, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response diff ered from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the presen t study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.