The bovine tick Rhipicephalus microplus is responsible for severe economic losses in tropical cattle production. Bos indicus breeds are more resistant to tick infestations than are Bos taurus breeds, and the understanding of the physiological mechanisms involved in this difference is important for the development of new methods of parasite control. We evaluated differences in the transcript expression of genes related to the immune response in the peripheral blood of cattle previously characterized as resistant or susceptible to tick infestation. Crossbreed F2 Gir x Holstein animals (resistant, N = 6; susceptible, N = 6) were artificially submitted to tick infestation. Blood samples were collected at 0, 24, and 48 h after tick infestation and evaluated for transcript expression of the CD25, CXCL8, CXCL10, FoxP3, interleukin (IL)-10, and tumor necrosis factor alpha (TNFα) genes. Gene expression of CD25 (6.00, P < 0.01), IL-10 (31.62, P < 0.01), FoxP3 (35.48, P < 0.01), and CXCL10 (3.38, P < 0.05) was altered in the resistant group at 48 h compared with samples collected before infestation. In the susceptible group, CXCL8 (-2.02, P < 0.05) and CXCL10 (2.20, P < 0.05) showed altered expression 24 h after infestation. CXCL8 (-5.78, P < 0.05) also showed altered expression at 48 h after infestation when compared with samples collected before infestation. We detected a correlation between T γδ cell activity and the immunological mechanisms that result in a higher resistance to R. microplus in cattle.